Is EEF1G p.Ala254Val (c.761C>T) pathogenic?

EEF1G p.Ala254Val (c.761C>T) is classified Uncertain significance in EEF1G (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). AlphaMissense: likely benign (0.0767); Ultra-rare (popmax 0.0121%, sas).

How common is EEF1G p.Ala254Val (c.761C>T) in the general population?

EEF1G p.Ala254Val (c.761C>T) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

What do computational predictors say about EEF1G p.Ala254Val (c.761C>T)?

AlphaMissense predicts likely benign (score 0.0767) — an in-silico prediction, not a clinical call.

EEF1G p.Ala254Val

c.761C>T · VCV3843484

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0767 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0767	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -7.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 7,832 bp · p 1.3e-10 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% South Asian · 11/91,068 alleles

Filtering AF 0.00676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.00291% 47/1,613,568 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0121%	8,279
European (non-Finnish)	0.00288%	34,700
Admixed American	0.00167%	59,988
African / African-American	0.00134%	74,890

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: EEF1G
Protein: p.Ala254Val
Coding: c.761C>T
MANE Select: NM_001404
Type: single nucleotide variant
Location: chr11:62566902 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.93 · 3 PDB
Residue 254: the 'disordered' region

Full EEF1G gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EEF1G p.Ala183Asp Uncertain significance ★ ⚠ same type
EEF1G p.Ala183Ser Uncertain significance ★ ⚠ same type
EEF1G p.Ala202Val Uncertain significance ★ ⚠ same type
EEF1G p.Ala269Val Uncertain significance ★ ⚠ same type
EEF1G p.Ala281Val Uncertain significance ★ ⚠ same type
EEF1G p.Ala2Val Uncertain significance ★ ⚠ same type
EEF1G p.Ala34Thr Uncertain significance ★ ⚠ same type
EEF1G p.Ala429Gly Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/eef1g-p-ala254val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown